Thin-slice reverse encoding distortion correction DWI facilitates visualization of non-functioning pituitary neuroendocrine tumor (PitNET)/pituitary adenoma and surrounding normal structures

Background To evaluate the clinical usefulness of thin-slice echo-planar imaging (EPI)-based diffusion-weighted imaging (DWI) with an on-console distortion correction technique, termed reverse encoding distortion correction DWI (RDC-DWI), in patients with non-functioning pituitary neuroendocrine tumor (PitNET)/pituitary adenoma. Methods Patients with non-functioning PitNET/pituitary adenoma who underwent 3-T RDC-DWI between December 2021 and September 2022 were retrospectively enrolled. Image quality was compared among RDC-DWI, DWI with correction for distortion induced by B0 inhomogeneity alone (B0-corrected-DWI), and original EPI-based DWI with anterior-posterior phase-encoding direction (AP-DWI). Susceptibility artifact, anatomical visualization of cranial nerves, overall tumor visualization, and visualization of cavernous sinus invasion were assessed qualitatively. Quantitative assessment of geometric distortion was performed by evaluation of anterior and posterior displacement between each DWI and the corresponding three-dimensional T2-weighted imaging. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient values were measured. Results Sixty-four patients (age 70.8 ± 9.9 years [mean ± standard deviation]; 33 females) with non-functioning PitNET/pituitary adenoma were evaluated. In terms of susceptibility artifacts in the frontal and temporal lobes, visualization of left trigeminal nerve, overall tumor visualization, and anterior displacement, RDC-DWI performed the best and B0-corrected-DWI performed better than AP-DWI. The right oculomotor and right trigeminal nerves were better visualized by RDC-DWI than by B0-corrected-DWI and AP-DWI. Visualization of cavernous sinus invasion and posterior displacement were better by RDC-DWI and B0-corrected-DWI than by AP-DWI. SNR and CNR were the highest for RDC-DWI. Conclusions RDC-DWI achieved excellent image quality regarding susceptibility artifact, geometric distortion, and tumor visualization in patients with non-functioning PitNET/pituitary adenoma. Relevance statement RDC-DWI facilitates excellent visualization of the pituitary region and surrounding normal structures, and its on-console distortion correction technique is convenient. RDC-DWI can clearly depict cavernous sinus invasion of PitNET/pituitary adenoma even without contrast medium. Key points • RDC-DWI is an EPI-based DWI technique with a novel on-console distortion correction technique. • RDC-DWI corrects distortion due to B0 field inhomogeneity and eddy current. • We evaluated the usefulness of thin-slice RDC-DWI in non-functioning PitNET/pituitary adenoma. • RDC-DWI exhibited excellent visualization in the pituitary region and surrounding structures. • In addition, the on-console distortion correction of RDC-DWI is clinically convenient. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s41747-024-00430-8.

A popular strategy for correction of geometric distortion in EPI-DWI involves acquiring pairs of images with reverse phase-encoding directions, known as "blip-up blip-down" acquisition, to generate an undistorted image.This off-console technique, available as the "topup" tool in FMRIB Software Library−FSL (https:// fsl.fmrib.ox.ac.uk/ fsl/ fslwi ki/ topup), can significantly improve extensive geometric distortion due to B 0 field inhomogeneity using the b = 0 s/mm 2 images with reverse phase-encoding directions [17,18].An off-console correction for distortion induced by eddy currents has also been reported [19].However, off-console techniques such as these require external post-processing and are therefore complicated to use in clinical practice.
Distortion correction techniques for EPI-based DWI have recently been implemented in clinical MRI scanners [20].A software package termed reverse encoding distortion correction DWI (RDC-DWI) has been developed [21,22], which is a novel on-console correction technique for distortion due to B 0 inhomogeneity and distortion induced by eddy currents.An on-console distortion correction technique of RDC-DWI is more convenient and clinically feasible compared with existing off-console distortion correction tools [17][18][19][20].
To the best of our knowledge, no previous study has evaluated the pituitary region on DWI employing an on-console distortion correction technique that uses pairs of images with reverse phase-encoding directions, such as RDC-DWI.This study aims to emphasize the clinical usefulness of thin-slice RDC-DWI by evaluating distortion, susceptibility artifact, and visualization of tumor and surrounding normal structures in patients with non-functioning PitNET/pituitary adenoma, in comparison with DWI with correction for distortion induced by B 0 field inhomogeneity alone (B 0 -corrected-DWI) and original EPI-based DWI with anterior-posterior phase-encoding direction (AP-DWI).

Patient study
To investigate clinical usefulness of thin-slice RDC-DWI in the pituitary region, patients with non-functioning PitNET/ pituitary adenoma were selected because non-functioning PitNET/pituitary adenoma is the most common pituitary tumor.Our institutional review board approved this retrospective study.Informed consent was waived due to its retrospective nature.A flowchart of the study design and patient inclusions is shown in

Phantom study
To evaluate the reproducibility and accuracy of RDC-DWI, apparent diffusion coefficient (ADC) values were compared among the three DWIs (AP-DWI, B 0 -corrected-DWI, and RDC-DWI) and the theoretical values using a Quantitative Imaging Biomarkers Alliance−QIBA DWI phantom (Model 128, High Precision Devices, Inc., Boulder, USA).The phantom contains 13 vials filled with 30 mL of polymerpolyvinylpyrrolidone (PVP) in an aqueous solution, in six concentrations of PVP (0%, 10%, 20%, 30%, 40%, and 50%) corresponding to the theoretical ADC values specified by the manufacturer.The phantom was used with the temperature maintained between -0.20 and 0.20 °C (ice water bath).

MRI parameters
All studies were performed using a 3-T MR (Vantage Centurian, Canon Medical Systems Corporation, Otawara, Japan) with a 32-channel head coil.The same technical parameters were used for the phantom study and human study.The imaging parameters for thin-slice RDC-DWI and 3D-T2WI are shown in Table 1.In addition, the b = 0 s/mm 2 images were scanned once for each phaseencoding direction and the b = 1,000 s/mm 2 images were scanned eight times for each phase-encoding direction with simultaneous motion probing gradients (MPGs) in three orthogonal directions.

RDC-DWI
RDC-DWI is an on-console distortion correction technique used in EPI-DWI.It corrects distortion induced by eddy currents by using the b = 1,000 s/mm 2 images with reverse phase-encoding direction after application of MPGs in addition to correcting distortion due to B 0 field inhomogeneity by using the b = 0 s/mm 2 images with reverse phase-encoding directions.
Generation of AP-DWI, B 0 -corrected-DWI, and RDC-DWI AP-DWI, B 0 -corrected-DWI, and RDC-DWI were generated on-console from the same raw data (Fig. 2).A shift map (B 0 ) was generated using the b = 0 s/mm 2 images with AP and PA phase-encoding directions.Shift maps (B 0 + Eddy) were generated using the shift map (B 0 ) and b = 1,000 s/mm 2 images with AP and PA phase-encoding directions after application of MPGs.AP-DWI was generated using the b = 0 s/mm 2 images with AP phaseencoding direction and b = 1,000 s/mm 2 images with AP phase-encoding direction without distortion correction.B 0 -corrected-DWI was generated using the b = 0 s/mm 2 images with AP and PA phase-encoding directions, b = 1,000 s/mm 2 images with AP phase-encoding direction, and shift map (B 0 ).RDC-DWI was generated using the b = 0 s/mm 2 images with AP and PA phase-encoding directions, b = 1,000 s/mm 2 images with AP and PA phaseencoding directions, and shift maps (B 0 + Eddy) for three orthogonal MPG directions.In practice, the on-console RDC-DWI generation processes after image acquisition took approximately 2:10 min:s.

Qualitative evaluation
The image qualities of b = 1,000 s/mm 2 images of the three DWIs (AP-DWI, B 0 -corrected-DWI, and RDC-DWI) were assessed for susceptibility artifact in the frontal and temporal lobes; anatomic visualization of the optic, oculomotor and trigeminal nerves; and overall tumor visualization using a 5-point Likert scale (0, very poor; 1, poor; 2, fair; 3, good; 4, excellent).Visualization of cavernous sinus invasion was assessed qualitatively using a 3-point Likert scale (0, poor; 1, fair; 2, good).Corresponding 3D-T2WI was used as the reference standard for assessing visualization of cavernous sinus invasion.The clinical course and surgical records were referred to when it was difficult to determine the extent of cavernous sinus invasion diagnosis using only 3D-T2WI.The criteria for image assessment are defined in Supplementary Figs.S1-S4.The evaluation was conducted by three board-certified neuroradiologists (S.Ok., S.Ot., and S.I., with 16, 13, and 8 years of experience in neuroradiology, respectively).The three DWIs were provided in random order, and each reader was blinded to the type of distortion correction method.The majority opinion of the raters was designated as the final value.If the three opinions differed, resolution was obtained by consensus.
Table 1 The imaging parameters for RDC-DWI and 3D-T2WI

Quantitative evaluation
Geometric distortion was determined as each of anterior and posterior displacement between each DWI and the corresponding 3D-T2WI in the sagittal plane using ITK-SNAP (http:// www.itksn ap.org/) (Fig. 3a-c) [23].To calculate SNR, contrast-to-noise ratio (CNR), and ADC value, regions of interest (ROIs) were placed on the pons and on a solid portion of the PitNET/pituitary adenoma on the b = 1,000 s/mm 2 image and the corresponding ADC map using ImageJ (https:// imagej.nih.gov/ ij/) (Supplementary Fig. S5).SNR was calculated as SI pons /SD pons , and CNR was calculated as (SI lesion − SI pons )/SD pons , where SI pons and SI lesion are mean signal intensity of the pons and the solid portion of the PitNET/pituitary adenoma, respectively, and SD pons is standard deviation of the pons.ROIs that including signal pileup artifacts were excluded for evaluating CNR and ADC value for PitNET/pituitary adenomas.
Evaluation of distortion and ROI measurements were performed by a board-certified radiologist (S.I.) and approved by another board-certified radiologist (S.Ok.).

Statistical analysis
Interrater reliability for image quality scores measured independently by the three radiologists was evaluated using Fleiss' κ statistics [24].The calculated κ statistic was interpreted as follows: ≤ 0.20, slight agreement; 0.21-0.40,fair agreement; 0.41-0.60,moderate agreement; 0.61-0.80,substantial agreement; and 0.81-1.00,almost perfect agreement.Image quality scores and measured displacements were compared among the three DWIs using the Friedman test followed by pairwise comparisons with Bonferroni correction because the results did not follow a normal distribution.SNR, CNR, and ADC values were also compared among the three DWIs using one-way repeated measures analysis of variance− ANOVA followed by pairwise comparisons with Bonferroni correction because these data followed a normal distribution.A p-value less than 0.050 was considered statistically significant.

Patient study Participants
Six patients with PitNET/pituitary adenoma with hemorrhage and 19 patients with no apparent residual tumor after surgery were excluded (Fig. 1).The remaining 64 patients (mean age, 70.8 ± 9.9 years [mean ± standard deviation]; 33 females) were evaluated and comprised 25 patients with unoperated clinically non-functioning PitNET/pituitary adenoma and 39 patients with residual non-functioning PitNET/pituitary adenoma after surgery.The demographics of all 64 participants are shown in Table 2.

Qualitative evaluation
Interrater reliability for qualitative evaluations was moderate to substantial agreement (κ = 0.59-0.78)(Supplementary Table S1).In 11 cases of cavernous sinus invasion, the diagnosis was determined with agreement of the three evaluators by also referring to the clinical course and surgical records because of difficulty using only 3D-T2WI.and Supplementary Fig. S7.

Quantitative evaluation
Anterior sagittal displacement due to geometric distortion was the least in RDC-DWI (median, 2.8 mm; interquartile range, 1.8-4.7 mm) (p < 0.001) and significantly lower in B 0 -corrected-DWI (3.8 mm; 2.4-5.5 mm) than in AP-DWI (7.4 mm; 4.3-10.5 mm) (p < 0.001).Posterior sagittal displacement was significantly lower in RDC-DWI (2.0 mm; 1.4-3.5 mm) and B 0 -corrected-DWI (2.6 mm; 1.6-3.9mm) than in AP-DWI (3.8 mm; 2.3-6.2mm) (p < 0.001).The measured value of posterior sagittal displacement was the least in RDC-DWI.There was no significant difference between RDC-DWI and B 0 -corrected-DWI (p = 0.065) (Fig. 3d).Table 4 lists the SNR, CNR, and ADC values.SNR was the highest in RDC-DWI and was significantly higher in AP-DWI (p < 0.001) than in B 0 -corrected-DWI (p = 0.001).After excluding 26 patients in whom ROIs contained signal pileup artifacts, CNR and ADC values of the solid portion of PitNET/pituitary adenomas were calculated in 38 patients.Among the three DWIs, CNR was the highest in RDC-DWI, and CNR was significantly higher in RDC-DWI than in B 0 -corrected-DWI (p < 0.001).There was no statistically significant difference in CNR between B 0 -corrected-DWI and AP-DWI (p = 1.000), or between RDC-DWI and AP-DWI (p = 0.094).There was no significant difference in ADC values of the pons or the solid portion of PitNET/pituitary adenomas among the three DWIs.

Phantom study
The b = 1,000 s/mm 2 images on RDC-DWI showed the fewest artifacts and least distortion among the three DWIs (AP-DWI, B 0 -corrected-DWI, and RDC-DWI) (Fig. 4b, c, and d).ADC values measured in each of the five PVP concentrations showed no significant difference among the three DWIs for concentrations of 0%, 30%, and 40% (Table 5).Statistically significant differences in ADC values were found at PVP concentrations of 10% and 20%; however, ADC values at these two concentrations on RDC-DWI were the closest to the theoretical ADC values provided by the manufacturer [25].

Discussion
The present study demonstrated that thin-slice EPI-based RDC-DWI with a novel on-console distortion correction technique enabled excellent visualization of the pituitary region and surrounding normal structures.Overall, RDC-DWI outperformed the other DWIs (B 0 -corrected-DWI and AP-DWI), exhibiting the best image quality in terms of susceptibility artifacts, geometric distortion, visualization of cranial nerves and cavernous sinus invasion, and overall tumor visualization.The excellent visualization on RDC-DWI results from its characteristic image acquisition and distortion correction.The on-console distortion correction technique of RDC-DWI is based on the b = 1,000 s/mm 2 images with reverse phase-encoding directions after application of MPGs in three orthogonal directions, in addition to the b = 0 s/mm 2 images with reverse phase-encoding directions.Therefore, RDC-DWI achieved combined correction of distortion due to B 0 field inhomogeneity and of eddy current-induced distortion.Moreover, the on-console distortion correction of RDC-DWI is more feasible in clinical practice than the existing off-console distortion correction tools [17][18][19][20].
In addition to reduction in susceptibility artifacts and distortion, RDC-DWI produced high-contrast images and had the highest SNR among the three DWIs   We also assessed the accuracy of RDC-DWI for visualizing cavernous sinus invasion by PitNET/pituitary adenoma, which has not been evaluated previously on DWI.Scores for visualization of cavernous sinus invasion were significantly better for RDC-DWI and B 0 -corrected-DWI than for AP-DWI.Based on our results, RDC-DWI and B 0 -corrected-DWI might visualize cavernous sinus invasion well even without contrast medium [27][28][29][30].With regard to postoperative cases in particular, RDC-DWI and B 0 -corrected-DWI can contribute to early detection and visualization of residual PitNET/pituitary adenoma in the cavernous sinus [5,31].Occasionally, residual Pit-NET/pituitary adenoma in the cavernous sinus can be difficult to assess on T2-weighted or contrast-enhanced T1-weighted images after surgery due to postoperative change [32]; however, RDC-DWI is better able to visualize residual PitNET/pituitary adenoma compared with other sequences because the venous pool of the cavernous sinus appears as a signal void on DWI.
Among the three DWIs, RDC-DWI showed the best visualization of both the trigeminal and right oculomotor nerves.This finding indicates that RDC-DWI had fewer susceptibility artifacts than B 0 -corrected-DWI, for the reason that susceptibility artifact is strongest where the cranial nerves pass near the paranasal sinuses.Anatomical visualization of the optic nerves was not superior on RDC-DWI, probably because the optic chiasma or optic nerves were compressed in more than half of the studied cases, and there might have been minimal air space between the optic nerves and the PitNET/pituitary adenomas.
The acquisition time for thin-slice RDC-DWI was 4:15 min:s.Scan times were also long in previously reported advanced DWI techniques for the pituitary region, such as line-scan DWI [8], periodically rotated overlapping parallel lines with enhanced reconstruction (PROPEL-LER)/BLADE DWI [9,10], turbo-spin-echo (TSE) DWI [12,13], and readout-segmented EPI-DWI [14,15], although parameters such as slice thickness, number of slices, field of view, and number of excitations were different from RDC-DWI.Scan time is longer for RDC-DWI than conventional EPI-DWI but is clinically acceptable considering the clinical usefulness of RDC-DWI in the pituitary region, as shown in this study.Distortion correction techniques with deep learning reconstruction might have potential to reduce scan time and improve image quality, although its usefulness and advantages remain unclear [33].
Our study has several limitations.First, we included images in both pre-and post-operative states.RDC-DWI seemed to have the best visualization both preoperatively and postoperatively, although we did not conduct a comparison.Second, we used 3D-T2WI as the reference in evaluating visualization of cavernous sinus invasion.Cavernous sinus invasion is generally diagnosed with contrast-enhanced T1WI [27,28,30,32]; however, many of the present patients did not undergo contrast-enhanced MRI.We referred to the clinical course and surgical records when it was difficult to determine the diagnosis using only 3D-T2WI.Finally, we included relatively considerable number of patients; however, more pre-and postoperative patients may be needed to generalize our results.Further evaluation in other pituitary lesions is also desirable.In addition, in our phantom study, the 50% PVP data were discarded due to air contamination.The other phantom study on RDC-DWI seems more reliable [22].
In conclusion, thin-slice RDC-DWI provided excellent image quality in terms of distortion, susceptibility artifact, and visualization of tumor and surrounding normal structures.RDC-DWI achieved accurate and high-contrast visualization with high spatial resolution, using an on-console combined correction for distortion due to B 0 field inhomogeneity and eddy current-induced distortion.Thin-slice RDC-DWI facilitates visualization of the pituitary region and surrounding normal structures even without contrast medium.

Fig. 1 .
Eighty-nine consecutive patients (mean age, 68.1 ± 11.4 years [mean ± standard deviation]; 44 females) with non-functioning PitNET/ pituitary adenoma who underwent MR imaging, including RDC-DWI with slice thickness of 1.2 mm and threedimensional T2-weighted imaging (3D-T2WI), between December 2021 and September 2022 were included.Patients were excluded if they met the following exclusion criteria: (a) PitNET/pituitary adenoma with hemorrhage and (b) no apparent residual tumor after surgery.

Fig. 2
Fig. 2 Schematic image of generation of shift maps (a) and generation of three DWIs: AP-DWI, B 0 -corrected-DWI, and RDC-DWI (b).Shift map (B 0 ) is generated using the b = 0 s/mm 2 images with anterior-posterior (AP) and posterior-anterior (PA) phase-encoding directions (a, yellow).Shift maps (B 0 + Eddy) are generated using the shift map (B 0 ) and the b = 1,000 s/mm 2 images with AP and PA phase-encoding directions after application of three orthogonal motion probing gradients (MPGs) (a, red, blue, and green).AP-DWI is an original EPI-based DWI without distortion correction (b, top).B 0 -corrected-DWI is generated using the b = 0 s/mm 2 images with both phase-encoding directions (AP and PA), the b = 1,000 s/ mm 2 images with AP phase-encoding direction, and the shift map (B 0 ) (b, middle).RDC-DWI was generated using the b = 0 s/mm 2 images with both phase-encoding directions (AP and PA), the b = 1,000 s/mm 2 images with both phase-encoding directions (AP and PA), and the shift maps (B 0 + Eddy) with MPGs in three directions (b, bottom).AP, Anterior-posterior; DWI, Diffusion-weighted imaging; EPI, Echo-planar imaging; MPG, Motion probing gradient; PA, Posterior-anterior; RDC-DWI, Reverse encoding distortion correction DWI

Fig. 3
Fig. 3 Measurement of anterior and posterior sagittal displacements.The contour of a PitNET/pituitary adenoma on three-dimensional T2-weighted imaging (3D-T2WI) in the sagittal plane (a) is superimposed on the corresponding reconstructed sagittal diffusion-weighted imaging (DWI) (c).Geometric distortion (b, arrows) is determined as anterior and posterior displacements between DWI and the corresponding 3D-T2WI (c).The boxplots show results of anterior and posterior sagittal displacements (d).Anterior sagittal displacement is the least in RDC-DWI and is significantly lower in B 0 -corrected-DWI than in AP-DWI.Posterior sagittal displacement is significantly lower in RDC-DWI and B 0 -corrected-DWI than in AP-DWI.3D-T2WI, Three-dimensional T2-weighted imaging; AP, Anterior-posterior; DWI, Diffusion-weighted imaging; EPI, Echo-planar imaging; PA, Posterior-anterior; PitNET, Pituitary neuroendocrine tumor; RDC-DWI, Reverse encoding distortion correction DWI

Fig. 5 A
Fig. 5 A 68-year-old woman with residual non-functioning PitNET/pituitary adenoma after surgery.Axial 3D-T2WI (a), axial b = 1,000 s/mm 2 images of AP-DWI (b), B 0 -corrected-DWI (c), and RDC-DWI (d) are shown.The residual PitNET/pituitary adenoma cannot be clearly distinguished from the right cavernous sinus on axial 3D-T2WI (a).There is severe distortion, susceptibility artifact, and signal pileup around the residual PitNET/ pituitary adenoma and the left trigeminal nerve on AP-DWI (b, arrows).B 0 -corrected-DWI and RDC-DWI depict undistorted residual PitNET/pituitary adenoma without apparent susceptibility artifact (c and d).Compared with B 0 -corrected DWI, there is less blurring on RDC-DWI, particularly in the sphenoid sinus (c, arrowheads), and there are fewer susceptibility artifacts in the left trigeminal nerve (c, arrow).3D-T2WI, Three-dimensional T2-weighted imaging; AP, Anterior-posterior; DWI, Diffusion-weighted imaging; PitNET, Pituitary neuroendocrine tumor; RDC-DWI, Reverse encoding distortion correction DWI Data are presented as the mean ± standard deviation a AP-DWI versus B 0 -corrected-DWI b AP-DWI versus RDC-DWI c B 0 -corrected-DWI versus RDC-DWI ADC Apparent diffusion coefficient, ADC PitNET/pituitary adenoma ADC value for the solid portion of pituitary neuroendocrine tumor (PitNET)/pituitary adenoma, ADC pons ADC value for the pons, AP Anterior-posterior, CNR Contrast-to-noise ratio, DWI Diffusion-weighted imaging, SNR Signal-to-noise ratio, PitNET Pituitary neuroendocrine tumor, RDC-DWI Reverse encoding distortion correction DWI

Table 2
Patient demographics

Table 3
Results of qualitative evaluations for AP-DWI, B 0 -corrected-DWI, and RDC-DWI

Table 4
SNR, CNR, and ADC values according to DWI type

Table 5
ADC values (× 10 -6 mm 2 /s) of PVP vials in the phantom study according to DWI type Data are presented as the mean ± standard deviation.The 50% PVP data were discarded because of air contamination a AP-DWI versus B 0 -corrected-DWI b AP-DWI versus RDC-DWI c B 0 -corrected-DWI versus RDC-DWI ADC Apparent diffusion coefficient, AP Anterior-posterior, DWI Diffusion-weighted imaging, PVP Polymerpolyvinylpyrrolidone, RDC-DWI Reverse encoding distortion correction DWI